Raghav Yamdagni

A chlorinated monoterpene ketone, acylated β-sitosterol glycosides and a flavanone glycoside from Mentha longifolia (Lamiaceae)

Mentha longifolia (Lamiaceae), an aromatic herb yielded a new halogenated chloro-derivative of menthone (longifone), two new derivatives of beta-sitosterol glycoside (longiside-A and -B) and a new flavanone-glycoside (longitin). The beta-sitosterol and flavanone glycosides were purified as their acetate derivatives. Structures of all the isolated constituents were elucidated with the aid of HMBC techniques. However, the structure of longifone was also determined through X-ray crystallography.

Steroid and Antibacterial Steroidal Glycosides from Marine Green Alga Codium Iyengarii Borgesen

The ethyl acetate soluble part of methanolic extract of marine green alga Codium iyengarii collected from Karachi coast of Arabian Sea afforded a new steroid ( 1 , iyengadione) and two new steroidal glycosides [iyengaroside-A ( 2 ) and B ( 3 )] along with clerosterol galactoside ( 4 ). Their structures were elucidated with the aid of 1D-NMR spectroscopy and reconfirmed through HMBC experiments. The bactericidal activity of 1 - 4 was also explored and found positive response from iyengaroside-A ( 2 ) and clerosterol galactoside ( 4 ).

The Design and Synthesis of a Potent Angiotensin II Cyclic Analogue Confirms the Ring Cluster Receptor Conformation of the Hormone Angiotensin II

The novel amide linked Angiotensin II potent cyclic analogue, c-[Sar1,Lys3,Glu5] ANG II 19 has been designed and synthesized in an attempt to test the aromatic ring clustering and the charge relay bioactive conformation we have recently suggested for ANG II. This constrained cyclic analogue was synthesized by connecting the Lys3 amino and Glu5 carboxyl side chain groups, and it was found to be potent in the rat uterus assay and in anesthetized rabbits. The central part of the molecule is fixed covalently in the conformation predicted according to the backbone bend conformational model proposed for Angiotensin II. The obtained results using a combination of 2D NMR, 1D NOE spectroscopy and molecular modeling revealed a similar Tyr4-Ile5-His6 bend, a His6-Pro7 trans configuration and a side chain aromatic ring cluster of the key aminoacids Tyr4, His6, Phe8 for c-[Sar1,Lys3,Glu5] ANG II as it has been found for ANG II (Matsoukas, J. H.; Hondrelis, J.; Keramida, M.; Mavromoustakos, T.; Markriyannis, A.; Yamdagni, R.; Wu, Q.; Moore, G. J. J. Biol. Chem. 1994, 269, 5303). Previous study of the conformational properties of the Angiotensin II type I antagonist [Hser(gamma-OMe)8] ANG II (Matsoukas, J. M.; Agelis, G.; Wahhab, A.; Hondrelis, J.; Panagiotopoulos. D.; Yamdagni, R.; Wu, Q.; Mavromoustakos, T.; Maia, H.; Ganter, R.; Moore, G. J. J. Med. Chem. 1995, 38, 4660) using 1-D NOE spectroscopy coupled with the present study of the same type of lead antagonist Sarilesin revealed that the Tyr4-Ile5-His6 bend, a conformational property found in Angiotensin II is not present in type I antagonists. The obtained results provide an important conformational difference between Angiotensin II agonists and type I antagonists. It appears that our synthetic attempt to further support our proposed model was successful and points out that the charge relay system and aromatic ring cluster are essential stereoelectronic features for Angiotensin II to exert its biological activity.

Detection of a new polymeric species formed through the hydrolysis of gallium(III) salt solutions

A previously unreported gallium species has been detected which is formed by the hydrolysis of aqueous gallium(III) solutions. N.m.r. studies have shown that this species has a tetrahedrally co-ordinated gallium nucleus whose chemical shift suggests that it is structurally analogous to the central tetrahedral aluminium occurring in the [AlO4Al12(OH)24(H2O)12]7+ cation. The size of the polymeric gallium species was estimated by measuring the increase in the basal (d001) spacing of a montmorillonite upon intercalation. The hydrated height of the gallium polymer in its orientation relative to the phyllosilicate sheets was found to be approximately 9.4 A, which is about 5.6% larger than the size of the Al13 cationic unit, measured by the same method. This compares well with geometric calculations which show that a Ga13 cationic species would be expected to be about 5.7% larger than the analogous aluminium species. These results suggest strongly that a [GaO4Ga12(OH)24(H2O)12]7+ cation forms during the hydrolysis of gallium(III) solutions at a pH range of approximately 3–4. The reason why this species has not been previously reported may be related to the fact that it appears to be much less stable in solution than the analogous aluminium species, as revealed by n.m.r. evidence.

II. 1H-NMR studies of sarmesin and [des1]sarmesin conformation in dimethylsulfoxide by nuclear Overhauser effect (NOE) enhancement spectroscopy: Folding of the N- and C-terminal domains

The conformational properties of the competitive angiotensin II antagonist sarmesin [Sar-Arg-Val-Tyr(Me)-His-Pro-Phe] and its heptapeptide analogue [des1]sarmesin in dimethylsulphoxide-d6 were investigated by nuclear Overhauser effect (NOE) enhancement studies. Assignment of all backbone and side-chain protons was possible by combining information from intraresidue NOE studies with two-dimensional correlated spectroscopy (COSY) studies. Saturation of the His C alpha proton of sarmesin produced essentially the same interresidue NOE enhancement of the two Pro C delta protons, illustrating the presence of the trans His-Pro bond. Saturation of the Sar N-methyl group caused enhancement of one of the His C beta protons, suggesting the presence of a turn in the N-terminal region of the molecule. Saturation of His C2 in sarmesin and [des1]sarmesin enhanced the Tyr(Me) methyl signal. Saturation of the Tyr(Me) methyl protons in [des1]sarmesin produced NOE enhancement of the His C2 and C4 protons, and saturation of the His C2 proton enhanced the Tyr(Me) meta and ortho proton signals. Interresidue interactions between the Tyr(Me) and His protons in sarmesin and [des1]sarmesin illustrate that these two side-chains remain in close proximity even in the absence of the postulated hydrogen bond between Tyr hydroxyl and the His imidazole ring in angiotensin II. The data suggest a preferred conformation for sarmesin in DMSO in which the peptide backbone is S-shaped and similar to that for angiotensin II.

Insights into the Chemical Biology of Selenium

The long-sought pathway by which selenocysteyl-tRNA[Ser]Sec is synthesized in eukaryotes has been revealed. Seryl-tRNA[Ser]Sec is O-phosphorylated and SecS, a pyridoxal phosphate-dependent protein, catalyzes the reaction of O-phosphoseryl-tRNA[Ser]Sec with monoselenophosphate to give selenocysteyl-tRNA[Ser]Sec . 1 H- 77 Se HMQC-TOCSY NMR spectroscopy has been developed to detect the selenium-containing amino acids present in selenized yeast after protease XIV digestion. An archived selenized yeast sample is found to contain the novel amino acid S-(methylseleno)cysteine in addition to selenomethionine. Arsenite and selenite react with GSH to form (GS) 2 AsSe−. The structure of this compound has been determined by EXAFS, 77 Se NMR and Raman spectroscopic and chromatographic studies. Its formation under biological conditions has been demonstrated.

Comparison of the hydrolyses of gallium(III) and aluminium(III) solutions by nuclear magnetic resonance spectroscopy

A quantitative 71Ga n.m.r. study of the base hydrolysis of gallium(III) salt solutions has been undertaken. The resulting spectra were very similar to the 27Al n.m.r. spectra obtained for aluminium solutions hydrolysed under analogous conditions. No evidence was observed of any species different from those seen for aluminium, despite the fact that the eventual outcomes of the hydrolyses are different, i.e. precipitation of an oxyhydroxide of diaspore structure in the case of gallium, and the eventual formation of a gibbsite hydroxide phase in the case of aluminium. For aluminium, the formation of the [AlO4Al12(OH)24(H2O)12]7+ tridecamer is well known, and the formation of an analogous species for gallium has also been proposed. Although the 71Ga n.m.r. studies undertaken herein appear to show that much less of the gallium polyoxycation is formed than is the case for aluminium, clay mineral pillaring studies have suggested that this apparent difference is not real. Through consideration of both the extremely broad nature of the tetrahedral gallium peak and the high quadrupole moment of the 71Ga nucleus, it is proposed that the gallium tridecamer is much more distorted than the aluminium species, and that the integrated area of the n.m.r. peak assigned to this species does not accurately represent the amount actually present in solution.

The thionophosphate–thiolophosphate photoisomerization proceeds predominantly through a non-chain radical pathway. Synthetically viable benzylation of tetrahydrofuran, propan-2-ol and olefins

The photoirradiation of thionophosphates, ROP(S)(OEt)2, derived from benzyl and vinylogously benzyl alcohols in CH3CN, with a Hanovia medium-pressure mercury lamp in a quartz vessel leads to the formation of the corresponding thiolophosphates, RSP(O)(OEt)2, through a non-chain radical pathway. This behavior of thionophosphates is unlike that of the related phosphates, which react through ionic dissociation–recombination processes. When the irradiation is conducted in solvents such as PriOH, THF and toluene, benzylation of these solvents takes place in synthetically respectable yields. Irradiation of thionophosphates in CH3CN leads to a convenient allylic benzylation of olefins.

Ga13, GaAl12, and Al13 Polyoxocations and Pillared Clays

Studies of the hydrolysis of aqueous gallium and mixed gallium/aluminum solutions have resulted in the synthesis of Ga13 and GaAl12 cations which are isostructural with the Al13 species which has been the principal ion utilized in clay mineral pillaring studies. These ions have been characterized through the use of solution NMR studies, as well as MAS NMR, powder X -ray diffraction and infrared investigations of their sulfate salts. Their relative stabilities in solution have been found to follow the order GAl3 << Al13 <<GaAl12, which also appears to correlate with the order of increasing symmetry of their overall structures.